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Define extracellular matrix

Complex network of proteins and carbohydrates filling spaces between cells
Comprises fibrillar and non-fibrillar components


List 4 functions of the ECM

Provides physical support
Determines mechanical and physicochemcial properties of tissue
Influences growth, adhesion and differentiation status of the cells and tissues with which it interacts
Essential for development, tissue function and organogenesis


What type of tissue is rich in ECM?

Connective tissue


What are the 3 main components of the ECM? Give examples of each.

Collagen: e.g. collagen type IV
Multi-adhesive glycoproteins: e.g. fibronectin
Proteoglycan: e.g. aggrecan


Which substances of ECM are only found in the basement membrane?

Collagen type IV


Give 5 examples where gene mutations affect ECM matrix proteins

Osteogenesis imperfecta: Type I collagen
Marfan’s syndrome: Fibrillin 1
Alport’s syndrome: Type IV collagen (alpha 5)
Epidermolysis Bullosa- Laminin 5 (in all 3 chains)
Congenital Muscular Dystrophy- Laminin 2 (alpha 2 chain)


Give 2 examples where gene mutations affect ECM catabolism

Hurler’s syndrome: L-alpha-iduronidase
Other “mucopolysaccharidoses” (inability to degrade GAGs)


Give 3 fibrotic disorders due to excessive ECM deposition

Liver fibrosis: cirrhosis
Kidney fibrosis: diabetic nephropathy
Lung fibrosis: silicosis


Give an example of a disorder due to excessive loss of ECM



Different types/ orientations of collagen give connective tissue varied properties

Tendon and skin: Tough and flexible
Bone: hard and dense
Cartilage: Resilient and shock-absorbing


Describe the arrangement of collagen fibres in skin and explain its significance.

Successive layers are at right angles to each other so it can resist tensile force in all directions


Variability of collagen

28 collagen types in humans
42 genes encoding collagens
Each collagen molecule comprises 3 alpha chains, forming a triple helix.
Can be composed of one or more different alpha chains


What is the structure of a collagen molecule?

Stiff triple helix consisting of 3 alpha chains
Every 3rd AA is glycine because only glycine is small enough to fit in the inside of the triple helix.
The other 2 AAs are commonly proline and hydroxyproline, which form interchain hydrogen bonding that contributes to the structural integrity of collagen


How long is each alpha chain in fibrillar collagen and what does this form?

1000 AAs long
Forms left-handed helix


Describe the biosynthesis of collagen.

Synthesised as pro-collagen which has 2 protruding pro-peptides, 1 at each end, which aren’t in triple helical form
In fibrillar collagen after secretion, pro-peptides are cleaved, so collagen can form cross-linkages with other collagen molecules to form collagen fibrils
Pro-peptides remain part of the collagen in most other types of collagen


What is the importance of hydroxylation of proline and lysine in collagen structure?

Allows interchain hydrogen bonding that contributes to the structural integrity and stability of the collagen fibre
Lysine and hydroxylysine are also modified in the formation of covalent cross-linkages after the collagen is secreted – this helps provide tensile strength and stability


What 2 other substances are needed for hydroxylation of proline and lysine?

Vitamin C


What does vitamin C deficiency result in?

Underhydroxylated collagens
Detrimental to tissue stability (scurvy).


How is collagen arranged in tendons?

Parallel bundles


What are the collagens that don't form fibrils?

Fibril-associated collagens (e.g. collagen IX) which is involved in the organisation of collagen fibrils
Network forming collagens (e.g. collagen) in basement membranes


Describe collagen type IV assembly

Assembled into a sheet-like network
= essential component of basement membranes


Describe the composition of Elastic fibres.

Elastin core
Microfibrils around the outside that are rich in fibrillin


What are elastic fibres important for?

Elasticity of tissues e.g. skin, blood vessels


How is the extent of stretching limited?

Collagen and elastin fibres are interwoven


What does the integrity of elastic fibres depend on?



What causes Marfan's syndrome and what are some clinical features of Marfan's Syndrome?

Gene mutation in fibrillin 1
Longer arm span than height
Long fingers and toes
Predisposed to aortic ruptures


What is the general structure of elastin?

Consists of hydrophobic regions and alpha-helical regions (rich in alanine and lysine)
Many lysine chains are covalently cross-linked


What are basement membranes?

Highly specialised ECMs containing distinct spectra of collagens, glycoproteins and proteoglycans.
Flexible, thin mats underlying epithelial sheets, tubes, muscle, fat and peripheral nerve cells
Regulate tissue function


What are basement membranes also known as?

Basal laminae


What does the BM in the kidney act as?

Highly selective filter